Some Research on Fragrances
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Listed in reverse date order:
Jansson 2001Strategy to decrease the risk of adverse effects of fragrance ingredients in cosmetic products.
Nair 2001Final report on the safety assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate.
Schafer 2001Epidemiology of contact allergy in adults.
Api 1999Evaluation of the oral subchronic toxicity of HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2 -benzopyran) in the rat.
Christian 1999Developmental toxicity studies of four fragrances in rats.
Lake 1999Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment.
Anderson 1998Acute toxic effects of fragrance products.
Kumar 1995Inhalation challenge effects of perfume scent strips in patients with asthma.
Ford 199090-day dermal toxicity study and neurotoxicity evaluation of nitromusks in the albino rat.
deGroot 1988The role of contact allergy in the spectrum of adverse effects caused by cosmetics and toiletries.
Gendler 1987Adverse reactions to cosmetics.
Spencer 1984Neurotoxic properties of musk ambrette.
Cammer 1980Uncoupling of oxidative phosphorylation in vitro by the neurotoxic fragrance compound acetyl ethyl tetramethyl tetralin and its putative metabolite.
Giovinazzo 1980Photoallergic contact dermatitis to musk ambrette. Clinical report of two patients with persistent light reactor patterns.
Spencer 1979Neurotoxic fragrance produces ceroid and myelin disease.





















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  1. Acute toxic effects of fragrance products. Anderson RC, Anderson JH. Archives of Environmental Health 1998 Mar-Apr;53(2):138-46
    " To evaluate whether fragrance products can produce acute toxic effects in mammals, we allowed groups of male Swiss-Webster mice to breathe the emissions of five commercial colognes or toilet water for 1 h. . . . The emissions of these fragrance products caused various combinations of sensory irritation, pulmonary irritation, decreases in expiratory airflow velocity, as well as alterations of the functional observational battery indicative of neurotoxicity. Neurotoxicity was more severe after mice were repeatedly exposed to the fragrance products. . . . In summary, some fragrance products emitted chemicals that caused a variety of acute toxicities in mice. "
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  2. Evaluation of the oral subchronic toxicity of HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2 -benzopyran) in the rat. Api AM, Ford RA. Toxicology Letters 1999 Dec 20;111(1-2):143-9
    "...(HHCB) is used in a wide variety of fragrances in consumer products. . . HHCB was added to the diet of rats at levels calculated to result in mean daily doses of 5, 15, 50 or 150 mg HHCB/kg. . . . No adverse effects were revealed from clinical examination or following extensive histopathological examinations. . . histopathological examination of the prostate, seminal vesicles, mammary gland and testes of males and ovaries, mammary gland, uterus and vagina of females was undertaken on all animals in all test groups. This examination did not reveal any evidence of hormonal effects. "

    (1) They ate the chemical; they did not inhale.
    (2) This chemical has been in use for years before this study showed no hormonal effects
    (3) This one also does not look at neurological development

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  3. Uncoupling of oxidative phosphorylation in vitro by the neurotoxic fragrance compound acetyl ethyl tetramethyl tetralin and its putative metabolite. Cammer W. Biochemical pharmacology. 1980 Jun 1;29(11):1531-5
    No abstract
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  4. Developmental toxicity studies of four fragrances in rats. Christian MS, Parker RM, Hoberman AM, Diener RM, Api AM. Toxicology Letters 1999 Dec 20;111(1-2):169-74
    "Four fragrances, .. . (AHTN), . . . (HHCB), musk ketone and musk xylene were tested for developmental toxicity in Sprague-Dawley rats . . . Treatment (gavage (tube feeding to stomach), 5 ml/kg) occurred on GDs (gestation days, or days of pregnancy) 7-17 and Caesarean-sectioning on GD 20. Based on the results of these studies, none of the four fragrances tested were more toxic in the conceptuses (unborn baby) than in the dams (mother rat). . . The results of this study indicate that under conditions of normal use, the tested fragrances do not pose a risk to human conceptuses. "

    They appear to have measured weight gain, bone structure, how many were living, and other major changes. They do not appear to have considered neurological development.

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  5. The role of contact allergy in the spectrum of adverse effects caused by cosmetics and toiletries. de Groot AC, Beverdam EG, Ayong CT, Coenraads PJ, Nater JP. Contact Dermatitis 1988 Sep;19(3):195-201
    "Of 982 female clients of beauticians interviewed, 254 (25.9%) claimed to have experienced adverse reactions to cosmetics and toiletries in the preceding 5 years. . . . 150 women were patch tested. In the European standard series, only a few positive reactions were seen to possible cosmetic allergens: . . . Cosmetic allergy was considered to be "proven" in 3 patients (2.0%), and "possible" in 7 (4.7%). It is concluded that contact allergy is responsible for a minority (less than 10%) of all reactions to cosmetics and toiletries. The majority of reactions are due to irritation from personal cleanliness products such as soaps, shampoos, bath foams and from deodorants, or worsening of pre-existing dermatoses such as seborrhoeic dermatitis and acne "

    A standard series of tests was used, so that the items that triggered reactions were not used. Yet they concluded these patients were not "really" allergic at all, but only irritated.

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  6. 90-day dermal toxicity study and neurotoxicity evaluation of nitromusks in the albino rat. Ford RA, Api AM, Newberne PM. Food and Chemical Toxicology 1990 Jan;28(1):55-61
    " Musk ketone, musk xylene, musk tibetene and moskene, synthetic musks used in fragrances, were applied dermally to rats in daily doses . . . The chemically related musk ambrette, a known neurotoxin in rats, was used as a positive control. While musk ambrette was clearly neurotoxic and caused testicular atrophy, as had been previously reported, the other compounds tested caused neither effect. The only effects of application of these materials were some organ weight changes at the higher doses, but these were not associated with histopathological changes in any of the tissues. . . . "
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  7. Subchronic inhalation studies of complex fragrance mixtures in rats and hamsters. Fukayama MY, Easterday OD, Serafino PA, Renskers KJ, North-Root H, Schrankel KR. Toxicology letters 1999 Dec 20;111(1-2):175-87
    ". . . With finished fragrance products, these mixtures may represent 100 or more fragrance raw materials (FRMs). . . . Major FRMs evaluated included benzyl acetate, coumarin, hydroxycitronellal, musk ketone, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-gamma-2-be nzopyran (HHCB) and phenyl ethyl alcohol. Groups of rats or hamsters were exposed by inhalation . . .for 4 h per day, 5 days per week for 6 or 13 weeks. For each of the fragrance products, the doses used generally represented a ten- to 100-fold exaggeration of levels expected to be achieved during typical use by consumers. . . Subchronic exposure to all fragrance mixtures resulted in no toxicologically significant effects on animal survival, behavior, body weights or weight gains, organ weights, or in hematology, clinical chemistry, or urinalysis parameters. No gross pathological or histopathological findings related to test material exposures were observed. These studies support the conclusions that the fragrance mixtures would not pose a hazard to product users based on repeated and exaggerated inhalation exposures of animals. "

    (1) They seem to have evaluated 6 chemicals and concluded that all 100 FRMs are safe
    (2) I have written to ask them what behaviors were observed and whether they collected any neurological data
    (3) The researchers are International Flavors & Fragrances Inc - apparently a fragrance manufacturer

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  8. Adverse reactions to cosmetics. Gendler E. Cutis 1987 Jun;39(6):525-6
    "Adverse reactions to cosmetics can be irritant or allergic and are most often caused by fragrances or preservatives. Preservatives include formaldehyde, formaldehyde releasers, and parabens. Other agents that cause allergy are paraphenylenediamine in hair dyes and toluene sulfonamide formaldehyde resin in nail polishes. "
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  9. Photoallergic contact dermatitis to musk ambrette. Clinical report of two patients with persistent light reactor patterns. Giovinazzo VJ, Harber LC, Armstrong RB, Kochevar IE. Journal of the American Academy of Dermatology 1980 Oct;3(4):384-93
    "Two male patients with photoallergic contact dermatitis to musk ambrette, ... are reported. Musk ambrette is a synthetic fragrance material commonly used in foods and cosmetics. The clinical distribution of lesions presented by these patients strongly suggested an adverse reaction to light. . . . Photopatch tests to musk ambrette were positive. . . . This report emphasizes that exposure to household or cosmetic products represents a potential source of contact photosensitivity. Patients presenting with dermatoses of unknown origin confined to the light-exposed areas should have fragrances considered as possible etiologic agents. "
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  10. Strategy to decrease the risk of adverse effects of fragrance ingredients in cosmetic products. Jansson T, Loden M. American Journal of Contact Dermatitis 2001 Sep;12(3):166-9
    "In spite of extensive self-regulation of the fragrance industry, fragrance ingredients are still major causes of allergic contact dermatitis. . . . Herein, we propose a simple strategy to decrease the risk of adverse effects of fragrance ingredients in cosmetic products. . . . (1) limit the concentration of fragrance compound in the products, (2) follow legislation and guidelines, (3) limit the concentration of a number of well-known sensitizing fragrance chemicals, and (4) limit the concentration of essential oils and materials with unknown composition. . . ."

    They have discovered that less is better. We believe that none is best.

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  11. Inhalation challenge effects of perfume scent strips in patients with asthma. Kumar P, Caradonna-Graham VM, Gupta S, Cai X, Rao PN, Thompson J. Annals of allergy, asthma & immunology 1995 Nov;75(5):429-33
    "Perfume- and cologne-scented advertisement strips are widely used. There are, however, very few data on the adverse effects of perfume inhalation in asthmatic subjects. . . . Twenty-nine asthmatic adults and 13 normal subjects were included in the study. . . . Pulmonary function studies were performed before and at 10, 20, and 30 minutes after challenges. RESULTS: Inhalational challenges using perfume produced significant declines in FEV1 (measurement of breathing ability) in asthmatic patients when compared with control subjects. No significant change in FEV1 was noted after saline (placebo) challenge in asthmatic patients. The percent decline in FEV1 was significantly greater after challenge in severely asthmatic patients as compared with those with mild asthma. Chest tightness and wheezing occurred in 20.7% of asthmatic patients after perfume challenges. . . . CONCLUSIONS: Perfume-scented strips in magazines can cause exacerbations of symptoms and airway obstruction in asthmatic patients. Severe and atopic (allergic) asthma increases risk of adverse respiratory reactions to perfumes. "
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  12. Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment. Lake BG. Food and Chemical Toxicology 1999 Apr;37(4):423-53
    "The metabolism, toxicity and results of tests for carcinogenicity have been reviewed with respect to the safety for humans of coumarin present in foodstuffs and from fragrance use in cosmetic products. . . . The maximum daily human exposure to coumarin from dietary sources for a 60-kg consumer has been estimated to be 0.02 mg/kg/day. From fragrance use in cosmetic products, coumarin exposure has been estimated to be 0.04 mg/kg/day. The total daily human exposure from dietary sources together with fragrance use in cosmetic products is thus 0.06 mg/kg/day. No adverse effects of coumarin have been reported in susceptible species in response to doses which are more than 100 times the maximum human daily intake. The mechanism of coumarin-induced tumour formation in rodents is associated with metabolism-mediated, toxicity and it is concluded that exposure to coumarin from food and/or cosmetic products poses no health risk to humans. "

    Only cancer risk, and liver & lung toxicity is considered in this study.

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  13. Final report on the safety assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. Nair B. International Journal of Toxicology 2001;20 Suppl 3:23-50
    " Benzyl Alcohol is an aromatic alcohol used in a wide variety of cosmetic formulations as a fragrance component, preservative, solvent, and viscosity-decreasing agent. Benzoic Acid is an aromatic acid used in a wide variety of cosmetics as a pH adjuster and preservative. Sodium Benzoate is the sodium salt of Benzoic Acid used as a preservative, also in a wide range of cosmetic product types. . . . Acceptable daily intakes were established by the World Health Organization at 5 mg/kg for Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. . . . No adverse effects of Benzyl Alcohol were seen in chronic exposure animal studies using rats and mice. Effects of Benzoic Acid and Sodium Benzoate in chronic exposure animal studies were limited to reduced feed intake and reduced growth. Some differences between control and Benzyl Alcohol-treated populations were noted in one reproductive toxicity study using mice, but these were limited to lower maternal body weights and decreased mean litter weights. Another study also noted that fetal weight was decreased compared to controls, but a third study showed no differences between control and Benzyl Alcohol-treated groups. Benzoic Acid was associated with an increased number of resorptions and malformations in hamsters, but . . . negative in two rat studies. Genotoxicity (cancer-causing damage to DNA) tests for these ingredients were mostly negative, but there were some assays that were positive. Carcinogenicity studies, however, were negative. Clinical data indicated that these ingredients can produce nonimmunologic contact urticaria . . . In one study, 5% Benzyl Alcohol elicited a reaction, and in another study, 2% Benzoic Acid did likewise. . . . Recognizing that the nonimmunologic reactions are strictly cutaneous, likely involving a cholinergic mechanism, it was concluded that these ingredients could be used safely at concentrations up to 5%, but that manufacturers should consider the nonimmunologic phenomena when using these ingredients in cosmetic formulations designed for infants and children. Additionally, Benzyl Alcohol was considered safe up to 10% for use in hair dyes. . . .Because of the wide variety of product types in which these ingredients may be used, it is likely that inhalation may be a route of exposure. The available safety tests are not considered sufficient to support the safety of these ingredients in formulations where inhalation is a route of exposure. Inhalation toxicity data are needed to complete the safety assessment of these ingredients where inhalation can occur. "

    Note that in 2001 it is known that these ingredients are inhaled, and it is NOT known if it is safe for you to inhale them, but you may continue to do so until proven otherwise.

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  14. Epidemiology of contact allergy in adults. Schafer T, Bohler E, Ruhdorfer S, Weigl L, Wessner D, Filipiak B, Wichmann HE, Ring J. Allergy 2001 Dec;56(12):1192-6 |||| Full text available on line
    "We aimed to determine the prevalence of contact sensitization in the general population and to investigate associations with important sociodemographic and medical characteristics. . . . RESULTS: At least one positive reaction was exhibited by 40.0% of the subjects, with reactions most frequently observed to fragrance mix (15.9%), nickel (13.1%), thimerosal (4.7%), and balsam of Peru (3.8%). Women were sensitized more often than men (50.2% vs 29.9%. . . CONCLUSIONS: It is concluded that contact allergy is influenced by sociodemographic parameters and plays an important role in the general population. "
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  15. Neurotoxic properties of musk ambrette. Spencer PS, Bischoff-Fenton MC, Moreno OM, Opdyke DL, Ford RA. Toxicology and Applied Pharmacology 1984 Sep 30;75(3):571-5
    " Musk ambrette (2,6-dinitro-3-methoxy-4-tert-butyltoluene), a nitro-musk compound widely used as a fixative in fragrance formulations and found to a lesser degree in flavor compositions, produces hindlimb weakness when administered in the diet or applied to skin of rats for periods up to 12 weeks. Underlying neuropathologic changes consist of primary demyelination and distal axonal degeneration (nerve damage) in selected regions of the central and peripheral nervous system. . . . "
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  16. Neurotoxic fragrance produces ceroid and myelin disease. Spencer PS, Sterman AB, Horoupian DS, Foulds MM. Science 1979 May 11;204(4393):633-5
    " Acetyl ethyl tetramethyl tetralin (AETT), a component of soaps, deodorants, and cosmetics, produces hyperirritability and limb weakness in rats repeatedly exposed to the compound. Brain, spinal cord, and peripheral nerves are discolored blue, show progressive neuronal ceroid degeneration, and develop spectacular myelin bubbling. (myelin wraps and protects certain nerve fibers) These neurotoxic properties of AETT provide the basis for industry's decision to withdraw the compound from consumer products. In addition, AETT offers the experimentalist a new probe to explore the etiology and pathogeneses of human ceroid and myelin diseases. "
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